P543: CONSECUTIVE DAY DOSING OF HIGH-DOSE CYTARABINE CONSOLIDATION OVER 3 DAYS IS FEASIBLE IN OLDER PATIENTS WITH ACUTE MYELOID LEUKEMIA
Authors: Rithin Nedumannil, Emily Batterham, Andrew Wei, Ashish Bajel
Journal: HemaSphere (2023)

Background: High-dose cytarabine (HDAC) is commonly administered as consolidation therapy to adult patients with newly diagnosed acute myeloid leukemia (AML) achieving complete remission (CR). Compared with alternate day HDAC-135 dosing (given on days 1,3 and 5), condensed regimens such as HDAC-123 (given consecutively for 3 days) are associated with faster hematological recovery, reduced infection rates and shorter periods of hospital stay without impacting survival in adults up to 60 years. However, data is lacking on the use of HDAC-123 in older patients with AML. Aims: We report our experience with a condensed HDAC-123 consolidation regimen as post-remission therapy with the goal of assessing feasibility in AML, including patients >60 years. We hypothesized that HDAC-123 would be an appropriate alternative consolidation option for patients otherwise fit to receive HDAC-135 therapy. Methods: All patients with newly diagnosed AML in first CR who received 1-3 cycles of HDAC-123 consolidation at The Royal Melbourne Hospital and Peter MacCallum Cancer Centre were included in the study if at least one cycle of intensive induction chemotherapy was delivered. Patients were stratified by age (>60 years or ≤60 years). HDAC 1-3 g/m2 twice daily was administered as an inpatient on days 1, 2 and 3 of each 28-day consolidation cycle. Prophylactic granulocyte colony-stimulating factor was given after completing chemotherapy to all patients within each treatment cycle. The primary endpoints were deliverability (average dose per cycle), tolerability (time to hematological recovery), resource utilization (length of hospitalization) and safety (cytarabine-induced fever, neurotoxicity, bacteremia intensive care unit [ICU] admission or early death). Results: From December 2020 to December 2022, 37 patients received HDAC-123: 12 (32%) were >60 years of age and 25 (68%) were ≤60 years. Median age at diagnosis was 67 years if >60 years and 41 years if ≤60 years. There were no significant differences between the age groups with respect to demographics or disease characteristics (Table 1). The average cytarabine dose was 12 g/m2 per cycle (range 6-18 g/m2) in the >60-year cohort and 16.4 g/m2 per cycle in the ≤60-year group (range 6-18 g/m2). Across all 3 cycles, median times to neutrophil and platelet count recovery were 15 and 23 days, respectively (Table 2). In the whole cohort, median duration of hospital stay for chemotherapy administration was 4 days while that for neutropenic monitoring was 9 days. No significant differences in tolerability or resource utilization were seen between the two arms except a reduced median time to neutrophil count recovery after cycle 1 in the ≤60 years arm (14 vs 17 days, P = 0.001). From a safety perspective, cytarabine-induced fever and bacteraemia were most frequently seen during cycle 1 (Table 3). Only 3 patients (8%), all ≤60 years old, required a change in dosing schedule: two (5%) due to renal impairment and one due to reversible cerebellar neurotoxicity. Early mortality rates were low and the overall incidence of adverse events was not significantly different between the two arms. Summary/Conclusion: HDAC-123 is well-tolerated and can be safely delivered to fit AML patients aged >60 years. The associated faster haematological recovery can lead to tangible reductions in hospitalisation periods. Larger prospective and randomised studies are required to confirm our findings and further refine the approach to post-remission therapy in this population.Keywords: Consolidation, AML, Cytarabine